20.500.12556/RUL-174743 Označevalci učinkovitosti in sistemskih zapletov imunoterapije s strupi kožekrilcev Biomarkers predicting efficiency and adverse systemic reactions of Hymenoptera venom immunotherapy Z analizo transkriptoma dveh dobro okarakteriziranih skupin bolnikov z uspešnim oziroma neuspešnim zdravljenjem z imunoterapijo s strupi kožekrilcev smo dokazali pomembno vlogo inhibicije molekularne poti NFκB in utišanje gena DUX4. Uspešna imunoterapija je povezana z utišanjem signalnih poti Th2 in Th17 ter alternativne signalne poti makrofagov v sinergiji z inhibicijo signalne poti PPAR. Predlagamo dva označevalca, ki značilno korelirata z uspešno VIT ne glede na čas vzorčenja in sta primerna za nadaljnje raziskave: transkripta C4BPA in RPS10-NUDT3. Analiza dinamike humoralnih in celičnih označevalcev je pokazala znižanje ravni specifičnih IgE, celokupnih IgE in nivoja bazalne triptaze ter zvišanje ravni specifičnih IgG4 pri obeh skupinah bolnikov ter med njima ne omogoča razlikovanja. Pomembno pa se skupini bolnikov z uspešno in neuspešno VIT razlikujeta v pojavnosti sistemskih stranskih učinkov in v občutljivosti bazofilcev za degranulacijo pri nižji koncentraciji strupa kožekrilcev. Ugotovili smo, da je različica p.D816V v genu KIT, določena v krvnih celicah, pomemben napovedni dejavnik za zaplete med imunoterapijo s strupom čebele ter pomemben napovedni dejavnik za neuspešno zdravljenje. Poudarjamo pomen rutinskega določanja različice p.D816V v genu KIT pred pričetkom imunoterapije s strupi kožekrilcev in pomembnost spremljanja bolnikov ves čas obravnave. Longitudinal transcriptomic profiling revealed the importance of inhibition of the NFκB pathway and the downregulation of DUX4 transcripts. Successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers. Longitudinal follow-up showed that the immune responses do not differ significantly between patients with successful VIT and treatment failure. Those responses were characterized by decreased sIgE, tIgE, and BST, whereas sIgG4 levels increased. The analyzed biomarker which correlated considerably with treatment failure was higher basophil sensitivity to allergen stimulation before VIT. Similarly, systemic adverse events during the build-up phase of VIT correlated with treatment failure. Additionally, KIT p.D816V was a significant predictor of systemic adverse events during honeybee VIT and a significant predictor of VIT failure after completing wasp VIT. These observations emphasize the importance of KIT p.D816V screening before starting honeybee and wasp VIT and the need for detailed monitoring of high-risk patients during VIT build-up and after VIT completion. Imunoterapija s strupi kožekrilcev označevalci učinkovitosti sekvenciranje RNA Hymenoptera venom immunotherapy biomarkers of efficiency RNA sequencing true false false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2025-10-09 10:51:49 2025-10-09 10:51:58 2025-11-28 03:52:15 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 267456 252662531 52830.pdf 52830.pdf 1 F702415CD4DDE46E09ADA79B82827D8C 406cb1ad5b31aeafe8f2ae9191fdc79656c58d4799c5dd29fd03f3e3880bddcc fb4bf8bf-a4ec-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=219621 Biotehniška fakulteta 0 0 0